Scientists at U of L's Brown Cancer Centre Harness Diphtheria Toxin and Immune Factor to Fight Melanoma

A team of researchers at the James Graham Brown Cancer Centre have discovered that a drug containing parts of the diphtheria toxin appears to prompt the immune system to recognize and kill cancer cells in patients with advanced melanoma (skin cancer).

Preliminary results of a phase II clinical trial, presented today at an international symposium in Prague, Czech Republic, showed that five out of seven patients with stage IV disease experienced significant regression or stabilization of both tumours and the spread of cancer.Jason Chesney, associate director for translational research at the Brown Cancer Centre, presented one of only 10 projects chosen from almost 800 peer-reviewed research presentations to be featured at the conference, sponsored by the European Organisation for Research and Treatment of Cancer, the National Cancer Institute and the American Association for Cancer Research. BCC deputy director John Eaton presented his team's research to the media yesterday.Chesney, who is also an assistant professor of medicine, told a news briefing that the team is seeing some exciting results in stage IV melanoma patients whose median life expectancy is normally only about eight months. All of the patients are still alive after 12 months and the phase II trial is continuing to examine the effectiveness of the drug – called denileukin diftitox – in patients with melanoma."The immune system that attacks cancer cells in humans depends on a balance between T cells, which recognize and attack tumour cells, and suppressive or regulatory T cells, which turn off activated immune cells in order to prevent autoimmune disease," explained Chesney.The team discovered that the drug targets and depletes these regulatory T cells, allowing particular T cells in the immune system known as CD8 + T lymphocytes to attack and kill the melanoma cells in mice. This success led to testing of the drug in human patients. Chesney and his colleagues gave seven patients with stage IV melanoma nine or twelve micrograms per kilogram of body weight daily for four days, every three weeks for four cycles. The five patients on the higher dose experienced significant regression of several metastatic tumours."To our knowledge, this is the only trial to study the effects of regulatory T cell depletion in human cancer patients. The results demonstrate that depleting these cells in patients with melanoma may allow the immune system to activate and successfully kill cancer cells. These patients have survived longer than the median average life expectancy of a patient with stage IV melanoma. We believe that, in the future, this approach to therapy may prove to be useful in all types of cancer," said Chesney. (Source: University of Louisville : Brown Cancer Centre : November 2006.)